The ethical issues are different at different research stages of drug discovery.At the preclinical trial phase,laboratory animals are indispensable.The medical animal ethics committees need to approve and supervise animal testing during the experiment whether it adheres to the principles of animal protection,animal welfare principles and ethicalprinciples.At the phase of clinical trials,the subject of drug is human.The medical ethics committee should take full account of the ethical issues arising from the special medicine,special populations and disease in the process of trial and formulate detailed and feasible clauses,thus to ensure the scientificity of the trial and the rights and interests of subjects and promote new drug discovery and integrate with international standards.

Objective To compare the characteristics between two kinds of 40Hz auditory evoked potentials and provide suitable index for clinical auditory test of low-frequency. Methods The potentials including 40Hz auditory event related potential of middle latency response(40Hz AERP-MLR) and 40Hz auditory event related potential of early latency response(40Hz AERP-ELR) from window and vertex were recorded in guinea pigs. Results The common characteristics of the potentials were good frequency response,easy identification and lower responsive thresholds.Amplitude of 40Hz AERP-ELR was higher and threshold was lower than 40Hz AERP-MLR,especially 0.5kHz tone burst,which was (14.15?6.06)dBnHL.In vertex,the threshold of 40Hz AERP-MLR was (43.50?9.65)dBnHL,which was higher than that in round window(P

Objective To investigate the long term clinical effect of unilateral and bilateral percutaneous vertebroplasty(PVP) on the treatment of single segment osteoporotic vertebral compression fractures (OVCFs).Methods A total of 95 patients with OVCFs were retrospectively investigated.Each patient completed Visual Assessment Score(VAS) and Short Form-36 (SF-36) questionnaires preoperatively and follow-up to the endpoints postoperatively to assess the long term effect of unilateral and bilateral PVP.Patients underwent unilateral PVP (44 cases),whereas others underwent bilateral PVP (51 cases).Results VAS of immediate postoperative score (2.69 ± 0.55),(2.50 ± 0.39) and the last follow-up score (2.63 ± 0.46),(2.48 ± 0.32) in both techniques of PVP were significantly lower than the preoperative score (7.56 ± 0.73),(7.45 ± 0.54) (t =1.895,1.801,all P ＜ 0.01).However,VAS score at each time point in the unilateral PVP and bilateral PVP showed no significant difference (P ＞ 0.05).The last follow-up SF-36 scores (84.92±2.88),(86.71 t 2.73) in unilateral PVP and bilateral PVP were significantly higher than the preoperative score (58.35 ± 2.69),(57.93 ± 2.45) (P ＜ 0.01).But each time point of the SF-36 scores in both groups showed no significant difference (P ＞ 0.05).Unilateral percutaneous vertebroplasty showed some advantages on operation time,radiation exposure and usage of bone cement.Meanwhile,the bone cement leakage and recurrence of OVCFs on the adjacent segment in the two groups presented no significance.Conclusion Both unilateraland bilateral PVP could benefit the long term outcome of OVCFs,with regard to the significant advantage of unilateral PVP on operation time,radiation exposure and usage of bone cement.

Objective To estimate the effect of glycoprotein (transmembrane) nonmetastatic melanoma protein B (GPNMB) on the proliferation and migration of as well as melanogenesis in melanoma cells.Methods The expression of GPNMB was detected by immunofluorescence assay in two melanoma cell lines M14 and G-361,as well as in primary human melanocytes.Then,the three kinds of cells each were classified into three groups:experimental group treated with small interfering RNA targeting GPNMB (GPNMB-siRNA),negative control group treated with the negative control siRNA,blank control group remaining untreated.Methyl thiazolyl tetrazolium (MTT) assay,transwell invasion assay and spectrophotometry were performed to evaluate cell proliferation activity,invasion potential and melanin levels,respectively.Statistical analysis was done using Student's t test.Results GPNMB was expressed in both melanoma cells and melanocytes.The transfection with GPNMB-siRNA down-regulated the mRNA and protein expressions of GPNMB in,and markedly suppressed the proliferation and migration of,melanoma cells.In detail,the proliferative activity (expressed as the absorbence value at 570 nm) of M14 and G361 cells was reduced by 35％ and 40％ respectively,the migration activity of M14 and G361 cells by 49％ and 51％ respectively,and the melanin levels in melanocytes,M14 cells and G361 cells by 73％,82％ and 69％ respectively,in the experiment group compared with those in the blank control group.Conclusions The siRNA-mediated silencing of GPNMB could effectively inhibit the proliferation of,invasion of and melanogenesis in melanoma cells,which suggests that GPNMB plays critical roles in the initiation and progression of melanoma.

Objective To explore the factors related to the tolerance to enteral nutrition (EN) in gastric carcinoma patients undergoing surgical treatment and the implementation strategy of EN.Methods Fifty-four patients with gastric carcinoma undergoing surgery from November 2011 to September 2012 in the Affiliated Hospital of Medical College of Qingdao University were enrolled.EN were applied with sequential and gradual strategies.The tolerance status to EN was recorded.Factors related to the patient tolerance to EN were analyzed using single-factor and multiple-factor Logistic regression analysis.The incidences of gastrointestinal symptoms during EN application were recorded.Results Among the 54 patients,49 (90.74％) patients could tolerate EN.Single-factor analysis and multiple-factor Logistic regression analysis both showed that tumor staging (single-factor analysis:x2 =7.287,P =0.007 ; multiple-factor analysis:t =2.559,P =0.014) and surgical approach (singlefactor analysis:x2 =7.825,P =0.005 ; multiple-factor analysis:t =2.254,P =0.043) were major factors affecting patient tolerance to EN.Among the patients tolerant to EN,abdominal distension (19/49,38.8％) was the major gastrointestinal symptom of EN.Conclusion The sequential and gradual EN application strategy is suitable for the patients with gastric cancinoma after surgery,and can be widely used in clinical practice.

10.3969/j.issn.2095-4344.2013.25.001

OBJECTIVENeonatal asphyxia is the third leading cause of neonatal death and main cause of long-term neurodevelopmental handicap throughout the world. Prevention is more important than treatment. Most previous reports are limited to retrospective investigations of the relationships between some prenatal risk factors and low Apgar scores. This study was designed to prospectively investigate the relationship between prenatal risk factors and neonatal asphyxia and the influence of single or multiple risk factors on the incidence of neonatal asphyxia, and examine significant risk factors for neonatal asphyxia.

METHODSFrom April 2002 through October 2004, a total of 10 376 live-born newborns were enrolled. Forty-six prenatal risk factors were investigated. Neonatal asphyxia was diagnosed based on the following four items: 1. 1-min Apgar score or=0.10 and p<0.05 as significant. The OR and 95%CI were calculated for each significant risk factor.

RESULTSOf the 10 376 newborns, 8 530 cases (82.21%) had 1-9 risk factors, and asphyxia occurred in 117 cases (1.13%) out of the 8 530 cases. In the 1 846 cases without risk factors, none had asphyxia (x2=25.6, p<0.01). The incidence of asphyxia increased with increasing numbers of risk factors, from 0.23% in newborns with one risk factor to 14.29% in newborns who had nine risk factors (r=0.96, p<0.01). Twelve significant risk factors identified were as follows: ominous fetal heart rate patterns (OR=17.1,95%CI:11.2-25.9), placenta abruption (OR=15.2, 95% CI: 4.5-51.8), maternal lung diseases (OR=11.5, 95% CI:1.4-91.3), fetal acidosis (OR=6.1, 95% CI:1.5-24.1), placenta previa (OR=5.0,95% CI:1.5-16.9), breech delivery (OR=4.5, 95% CI: 2.1-9.9), meconium stained amniotic fluid (OR=3.2, 95% CI:2.2-4.8), forcepsjassisted delivery (OR=3.2, 95%CI: 1.1-9.9), prolonged labor (OR=2.94, 95%CI:1.5-5.8), abnormal utero contraction (OR=2.8, 95% CI:1.7-4.6), and premature delivery (OR=2.5,95%CI:1.4-4.8). Cesarean section had a protective effect (OR=0.6, 95% CI:0.4-0.9) (all p<0.05).

CONCLUSIONSIt is very important to prevent perinatal asphyxia by systematically examining prenatal risk factors and giving interventions for the newborns with risk factors, especially those with the above significant risk factors or with multiple risk factors. Proper cesareon section according to indications might be helpful to decrease the incidence of birth asphyxia.

Asphyxia Neonatorum ; etiology ; Female ; Humans ; Infant, Newborn ; Male ; Prenatal Care ; Risk Factors

OBJECTIVETo evaluate the therapeutic effect and safety of pelvic methotrexate (MTX) injection via the posterior fornix for treatment of tubal pregnancy.

METHODSNinety-six patients with tubal pregnancy (mean age 21-40 years) were randomized into 3 groups for treatment with pelvic MTX injection via the posterior fornix+mifepristone+traditional Chinese medicine (experiment group), intramuscular MTX injection+mifepristone+traditional Chinese medicine (control group I), or mifepristone+traditional Chinese medicine (control group II). On days 4 and 7 of the treatment, blood β-HCG of the patients in different groups was detected, and in cases with continuous reduction of blood β-HCG or a reduction by over 15%, β-HCG was checked every week. One week after the treatment, the size of the mass was measured by B-mode ultrasound. The clearance time of β-HCG and the hospital stay of the patients were recorded.

RESULTSTwenty-nine patients in the experimental group were treated successfully, with a cure rate of 90.6%, which was significantly higher than those in the two control groups (P<0.05). The clearance time of β-HCG and hospital stay were also much shorter in the experimental group (P<0.05).

CONCLUSIONPelvic MTX injection via the posterior fornix is a convenient procedure associated with minimal complications and serves as a good alternative for treatment of tubal pregnancy.

Abortifacient Agents, Nonsteroidal ; administration & dosage ; Adult ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Injections ; Methotrexate ; administration & dosage ; Mifepristone ; administration & dosage ; Pelvis ; Phytotherapy ; Pregnancy ; Pregnancy, Tubal ; drug therapy ; Vagina ; Young Adult

Higher alcohols are one of the main by-products of Saccharomyces cerevisiae in brewing. High concentration of higher alcohols in alcoholic beverages easily causes headache, thirst and other symptoms after drinking. It is also the main reason for chronic drunkenness and difficulty in sobering up after intoxication. The main objective of this review is to present an overview of the flavor characteristics and metabolic pathways of higher alcohols as well as the application of mutagenesis breeding techniques in the regulation of higher alcohol metabolism in S. cerevisiae. In particular, we review the application of metabolic engineering technology in genetic modification of amino transferase, α-keto acid metabolism, acetate metabolism and carbon-nitrogen metabolism. Moreover, key challenges and future perspectives of realizing optimization of higher alcohols metabolism are discussed. This review is intended to provide a comprehensive understanding of metabolic regulation system of higher alcohols in S. cerevisiae and to provide insights into the rational development of the excellent industrial S. cerevisiae strains producing higher alcohols.
Alcoholic Beverages ; Alcohols/analysis* ; Fermentation ; Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism*

Yarrowia lipolytica is a non-conventional yeast with unique physiological and metabolic characteristics. It is suitable for production of various products due to its natural ability to utilize a variety of inexpensive carbon sources, excellent tolerance to low pH, and strong ability to secrete metabolites. Currently, Y. lipolytica has been demonstrated to produce a wide range of carboxylic acids with high efficiency. This article summarized the progress in engineering Y. lipolytica to produce various carboxylic acids by using metabolic engineering and synthetic biology approaches. The current bottlenecks and solutions for high-level production of carboxylic acids by engineered Y. lipolytica were also discussed, with the aim to provide useful information for relevant studies in this field.
Carboxylic Acids/metabolism* ; Metabolic Engineering ; Synthetic Biology ; Yarrowia/metabolism*